We're in the midst of the second national Toxic Anterior Segment Syndrome outbreak in six months, as surgical centers across North America struggle to deal with the serious and potentially irreversible eye injury that results when a noninfectious toxic agent enters the anterior segment during surgery and causes an inflammatory reaction.

Our investigation is underway to determine the cause of this latest outbreak of TASS. At this point, we don't know what it is. Here's what you need to know to recognize, treat and avoid TASS.

So far, we're stumped
Reports of patients with suspected TASS have increased tenfold since March. We've been receiving 10 to 12 calls a day here at the Intermountain Ocular Research Center in Salt Lake City, Utah. In comparison, since we opened the center about 18 years ago to investigate post-operative inflammation and infection, we received an average of one to two phone calls a week with a question or problem.

Before this rash of TASS, the outbreaks we investigated were isolated. We'd send out a protocol asking the center what medications it had used, how it cleaned its instruments, how it prepped the patient for surgery and so on. We found outbreaks existed for many reasons - centers either used medications with preservatives or found residue on the instruments, for example.

When we see an outbreak that spreads coast to coast and across country borders, such as this one, it's more troubling. We have to try to find a common denominator between all of the cases. At the moment, we don't know what that is. We've got suspicions of several different products that may be contributing to the outbreak, but haven't determined anything definitive yet. Company representatives have also been helping in the analysis of these early reported cases.

We do know that it's not associated with the outbreak that occurred last fall when endotoxins contaminated certain lots of balanced salt solution manufactured by Cytosol Ophthalmics. The FDA received complaints related to injuries in more than 300 patients who were given the BSS in question. That outbreak appeared to subside by early 2006 following a federal recall of the product. We suspect this latest outbreak began in March.

The cases we're seeing generally appear to be moderate: There's inflammation of the anterior chamber the first day post-op with no reported pain and vision still fairly good. Most of these patients aren't having significant corneal edema - the effect of more serious cases (see "How Bad Is Your TASS?" on page 63 for varying severities).

Right now, we're gathering as much data as quickly as possible to determine the etiology of the outbreak. As soon as we have more evidence, we plan to circulate it as rapidly as we can.

Often, you won't know of the inflammation at the time of surgery; you'll learn the next day in the clinic. By then, everything that you used for the surgery is tossed out. We ask you to keep detailed records with your surgeries. Carefully note the lot numbers, exact solutions and cartridges you use for each patient. Our follow-up would be helped if there were an outbreak to investigate.

Just what is TASS?
The suspected causes of TASS are numerous and varied, including

• incorrect pH or osmolality of the balanced salt solution,
• preserved medications, including epinephrine, lidocaine and antibiotics,
• an antibiotic injected into the eye at the wrong concentration,
• endotoxin contamination of instruments,
• residue from phacoemulsification hand pieces,
• viscoelastic or detergents inside a reusable instrument or cannula, and
• aluminum hydroxide polishing compound residue on an IOL.

Often times, TASS is misidentified - and mistreated - as infectious endophthalmitis because symptoms of the two conditions overlap.

Mild cases get better in a couple of weeks without treatment; many of those likely go unknown. Severe cases can do real harm including permanent damage to the corneal endothelium, permanently fixed, dilated pupils or possible chronic glaucoma.

The best treatment is prevention. Once the toxic agent enters the eye and causes damage, there's little you can do other than suppress the secondary inflammatory immune response.

Patients with TASS will commonly complain of blurry vision, some ocular pain and eye redness following cataract surgery. Its rapid onset helps differentiate it most from infectious endophthalmitis, which most commonly shows up three to four days post-operatively. Most patients with TASS will develop symptoms within 12 to 24 hours of surgery. Other typical hallmarks of TASS are that it's limited to the anterior segment of the eye, it's always Gram stain and culture negative, and it improves with steroid treatment.

Besides its delayed onset, infectious endophthalmitis causes pain in 75 percent of patients, leads to lid swelling, conjunctival chemosis and discharge as well as diffuse ocular injection.

TASS patients could show signs of diffuse corneal edema, and they may also show signs of iris atrophy with pupillary abnormalities and eventual increased intraocular pressure.

There have also been several instances of delayed-onset TASS, too. There have been cases reported that occurred one to 21 days post-operatively.

TASS breeding grounds
While there are many different causes of TASS, here are some of the most common things to avoid:

• Preservatives. The corneal endothelium is especially sensitive to preservatives commonly used in topical ocular medications. Make sure any medication you inject into the eye is preservative free. You have to be especially aware - we've known cases where surgeons thought they were using preservative-free medications, but unbeknownst to them, their staff had switched to less expensive medication that included preservatives.

Studies show several reported cases of TASS were caused by inadvertent intraocular use of Alcon's Eye Stream, an eye rinse for external use only that is preserved with benzalkonium chloride (also known as BAK) 0.01%. Another study showed significant corneal edema and endothelial damage resulting from a viscoelastic containing BAK. If used chronically and on a frequent basis, normal concentrations of BAK in ocular mediations could cause harm.

• Additional irrigating solutions. Incorrect pH or osmolality of the BSS has also led to many TASS cases. In February, the FDA issued a federal recall of all brands and sizes of BSS that Cytosol Ophthalmics manufactured because product lots were found to have elevated levels of endotoxin. The outbreak seemed to subside after the recall.
• Sterilization issues. Any substance used in cleaning and sterilizing ophthalmic instruments may cause TASS. Detergents may accumulate as deposits and, eventually, residues on the inner and outer surfaces of reusable instruments. Most commonly, reusable instruments contain residual viscoelastic material. Most autoclaves don't reach a temperature high enough (140'C) to deactivate the enzymes or other active ingredients in the detergents.

The only effective way to remove detergent deposits from reusable instruments immediately after cleaning is by flushing instruments with adequate amounts of sterile deionized water. Each port of the I/A tips should be flushed with 120cc of sterile deionized water, for example. We've gotten so effective as physicians and surgical centers that we do cases so rapidly and sometimes don't take enough time to flush out the instruments all the way.

Outbreaks are also related to endotoxin contamination of instruments during sterilization. Water baths, ultrasound baths and even autoclave reservoirs - particularly those that aren't changed regularly - may harbor Gram-negative bacteria.

Also, don't reuse cannulas. Oxidized metal deposits and residues could form on reusable surgical tubing or metal hubs of the cannulas when you use plasma gas sterilization.

• Antibiotics. Toxicity from antibiotic agents most commonly occurs when you use them in irrigating solutions or inject them into the anterior segment at the conclusion of surgery to prevent endophthalmitis. However, prophylactic intracameral antibiotic agents aren't currently routinely recommended for endophthalmitis prophylaxis after cataract surgery. The risk for toxicity or complications is high and they haven't been shown to reduce endophthalmitis rates.
• Poor water. The quality of your water could cause a TASS outbreak. Reported cases showed an autoclave steam generator that had been supplied with softened city water led to sulfate water impurities that caused an outbreak. It turned out that the water wasn't flushed and drained as frequently as it has been in the past and as often it should have been.

In the event of an outbreak
You can control the inflammation from TASS with an intense topical corticosteroid drop. To ensure that the inflammatory condition is stabilizing, start your patient on a regimen of prednisolone acetate 1% drops every one to two hours, especially during the first days of use.

Also, carefully watch that your patient isn't developing cornea edema or significant intraocular pressure.

Anterior chamber washout isn't routinely recommended for treatment of TASS because the maximum damage to the anterior segment has likely already occurred.

Your entire surgical team should know what is appropriate for use in the eye - especially those who are cleaning and sterilizing ophthalmic instruments. They should also be vigilant when ordering any agent that will be used in the eye during anterior segment surgery.

Keep reusable instrument use to a minimum and thoroughly rinse those instruments that aren't disposable at the conclusion of each cleaning step with sterile, deionized water. Replace ultrasound baths daily since dirty bath water often grows Gram-negative bacteria.

An outbreak of TASS in your surgical center is an environmental and toxin control issue that requires complete analysis of all medications and fluids used during surgery.

If all that fails, remember there are resources available to you to aid in investigating outbreaks of TASS to help find the etiology of these cases and eliminate potential sources of post-operative inflammation.